pemigatinib and immune checkpoint inhibitor treated fgfr1/2/3 alteration advanced solid tumor

Conditions: Urothelial Carcinoma; Breast Neoplasms; Lung Cancer; Gastric Cancer; Soft Tissue Sarcoma; Other Carcinoma

Summary: this prospective phase il study is aim to evaluate the efficacy and safety of fgfr inhibitor combined with immune checkpoint inhibitors in fgfr1/2/3 variant advanced solid tumors.


Eligibility criteria:
inclusion criteria: * age ≥ 18 years; * histologically or cytologically confirmed unresectable advanced solid tumors with failure or intolerance to standard treatments; * at least one measurable lesion per recist v1.1 criteria; * gene testing confirms fgfr1/2/3 variants, including but not limited to mutations, fusions/rearrangements in solid tumors; * patients have not previously used specific small molecule multi-target inhibitors of the fgfr pathway, as assessed by investigators, and have been treated with immune checkpoint inhibitors; * ecog performance status of 0-1; * expected survival time \> 3 months; * laboratory criteria: 1. absolute neutrophil count (anc) ≥ 1.5 x 10⁹/l in the past 14 days without granulocyte colony-stimulating factor; 2. platelets ≥ 100 x 10⁹/l without transfusion in the past 14 days; 3. hemoglobin \> 9 g/dl in the last 14 days without transfusion or erythropoietin; 4. total bilirubin ≤ 1.5 x upper limit of normal (uln), or total bilirubin \> uln but direct bilirubin ≤ uln; 5. ast, alt ≤ 2.5 x uln (≤ 5 x uln in patients with liver metastasis); 6. serum creatinine ≤ 1.5 x uln and creatinine clearance (cockcroft-gault) ≥ 50 ml/min; 7. good coagulation function, defined as inr or pt ≤ 1.5 x uln. if on anticoagulant therapy, pt should be within the therapeutic range of anticoagulants; * female subjects of reproductive age must have a negative urine or serum pregnancy test within 3 days prior to the first dose (cycle 1, day 1). if the urine test is inconclusive, a blood test is required. non-reproductive females are defined as post-menopausal for at least one year or surgically sterile; * subjects with reproductive potential must use contraception with an annual failure rate of less than 1% during treatment and for 120 days after the last study drug dose (or 180 days after the last chemotherapy dose). exclusion criteria: * diagnosis of other malignancies within 3 years before the first dose, except for certain treated skin carcinomas and in-situ carcinomas; * previous treatment with selective fgfr inhibitors; * receipt of other investigational drugs within 21 days or antitumor drugs within 14 days before the first dose; * unresolved toxicity from prior treatments unless ≤ grade 1 or related to alopecia or fatigue; * known symptomatic cns metastasis or carcinomatous meningitis. stable patients post-treatment with no evidence of progression may be eligible if steroid-free for at least 14 days; * history of allogeneic organ or hematopoietic stem cell transplantation; * abnormal laboratory parameters: 1. serum phosphate \> 1.5 x uln; 2. elevated serum calcium or albumin-adjusted calcium outside the reference range; * known hiv infection or positive hiv test; * active or poorly controlled serious infection; * need for drainage treatment for pleural effusion, ascites, or pericardial effusion; * active hepatitis b or c infection with high viral load, or positive hbsag or anti-hcv antibodies. patients on antiviral therapy must meet lower thresholds; * significant uncontrolled heart disease, including recent mi, severe heart failure, or uncontrolled arrhythmias; * clinically significant ecg changes or history of significant cardiac issues; screening qtcf interval \> 480 ms, or jtc interval if applicable, must be ≤ 340 ms; * uncontrolled hypertension despite treatment; * hepatic encephalopathy, hepatorenal syndrome, or child-pugh grade b or higher cirrhosis; * major surgery within 4 weeks before the first dose or planned major surgery during the study; * unresolved complications from prior surgery; * pregnant or breastfeeding women, or those planning to become pregnant during the study period and for safety follow-up; * radiotherapy within 4 weeks before the first dose, except for non-cns palliative radiotherapy with a 2-week washout period; * history of systemic electrolyte imbalance or ectopic soft tissue calcification; * clinically significant corneal or retinal disease; * use of potent cyp3a4 inhibitors or inducers within 14 days or 5 half-lives before the first dose;

Keywords: pemigatinib fgfr1/2/3 alteration solid tumor